An Enzymic Disorder in the Erythrocytes of Paroxysmal Nocturnal Haemoglobinuria: a Deficiency in Acetyl‐cholinesterase Activity

THE abnormality which results in the short potential life-span of the red cells in paroxysiii‘il nocturnal haemoglobinuria (PNH) and in their susccptibility to haeniolysis by normal serum, is still vcry poorly understood. However, Dc Sandre, Ghiotto and Mastella (1956b) observcd in a PNH paticnt a red-ccll acetylcholinestcrase activity significantly lower than that found in normal adults, in patients with different kinds of haemolytic and non-haemolytic anacniias and in the paticnt’s mother. They suggcsted that such enzymic altcration might be related to the hacmolytic process, and they put forward an hypothesis based on thc rcsearch of Lindvig, Greig and Petcrson (195 I) on the relationship between acetylcholinesterasc activity and pcrnieability of red cells. Formijne, Poulic and Rodbard (1957) estimated thc red-cell cholesterol and phospholipids, both total and fractionated, in a PNH patient. Thcy found an increase in total cholcstcrol and phospholipids, which they ascribed to the greater corpuscular volume. Thc ratio betwccii lecithins, cephalins and sphingolipids was found to be normal. On the other hand, Harris, Prankerd and Westerniaii (1957) found in six PNH patients ‘1 significant increase in red-cell cholesterol and lipid nitrogen; niorcover, they noticed J significant iiicrcase in the ratio between phosphatidylscrine and pliosphatidylcholinc in the corpuscular stronia, due to an increase of the former and a diminution of thc lattcr. More recently, Barry (1959) re-investigated four of the six patients of Harris and his associates, employing other methods for thc red-cell phospholipid detection, and found a normal ratio between the cholinc-containing phospholipids (sphmgomyelin and lccithin) and the ‘ccphalin’ phospholipid fraction. Vaccari and Baldini (1958) discovered in a PNH patient a normal quantity of ‘reactive reduced thiol groups’, and a diminution of the ‘masked thiol groups’ (so callcd because tlicy becanie evident only after denaturation of the protein). Aerobic and anaerobic glycolysis of thc red cells was increascd, while the acetylcholincsterase activity was slightly reduced ; catalasc activity was dirninishcd proportionately to the number of circulating red cclls. De Sandrc and Ghiotto (1958) coniniuiiicatcd morc data obtained from the PNH case they had previously studied. The anaerobic glycolysis was normal; thc cholincstcrasc activity was decreased even when a specific substrate such as acctyl-P-mcthylcholinc was used. Moreover, thc prcseiicc of frcsh or inactivated scrum (56” C. for 30 minutes) did not influence the ciizyiiiic activity. In this paper wc report the cstimation of red-cell cholinestcrase activity in six morc PNH patients (sec Tablc I, Cases 2, 3, 4, 5 , 6 and 7). Cases 2 and 3 were paticnts admitted to our wards; Cases 4, 5 , 6 and 7 wcre under the care of Professor J. V. Dacie, who kindly Ict us have blood samplcs from them. Table I also contains the data, previously published, obtained from our first PNH paticnt (Case I). In each of the first three cases it was possible to determine the cholinesterasc activity of red cells from members of the patient’s family. * Director: Professor G. Patrassi.